Both malignant melanoma and nevi (moles) arise from melanocytes, and in many cases, nevi are thought to be intermediate in the pathway from melanocyte to melanoma. The presence of nevi is the strongest predictor of melanoma risk, and individuals who have higher numbers of nevi have an estimated 6 to 7-fold increased risk of developing malignant melanoma. Most nevi are developed in childhood and an understanding of the genetic, environmental, and behavioral factors that contribute to nevus development and growth is essential for understanding the pathways to melanoma. This study began in 1998 with a sun protection intervention study of newborns, in which sun exposure and sun protection data were collected beginning at birth and nevus exams were conducted starting at age 3. In 2004, additional children were added to the cohort, for which sun exposure, sun protection, and skin exam data were collected annually at ages 6-10. This study is now the longest running annual longitudinal study of childhood nevus development in the world. The overall aim of this project is to continue studying this cohort (n=936) with nevus counts and interviews for five additional years, from 2010 - 2014, and to add two new data collection components: a genetic component and more detailed data collection on changes in growth and shape of individual nevi. Previous research indicates that the 12 - 16 age range covered by the 2010 - 2014 funding period will be the most critical period for emergent nevi during the lifespan. This study will examine increases in number of nevi, and changes in individual nevi, and how these are influenced by the interaction of genes, UV exposure, and sun protection behavior during this critical period. Up to 100 SNPs in genes already known to be associated with nevi or identified recently through genome wide studies (conducted by other researchers) as related to pigmentation, nevus development, or melanoma will be assessed. The comprehensive nature of the data collected through age 10, the data that will be collected during the course of the proposed study, and the availability of newly described genes that influence human pigmentation, nevus development and melanoma will allow for the most complete analysis of influences on nevus formation yet undertaken. The long-term clinical and public health significance of this research include: 1) a better understanding of the biological mechanisms that result in both nevus and melanoma development, which could lead to new treatments for melanoma; 2) possible chemo-preventive agents to prevent nevus development and/or melanoma; and 3) more targeted public health recommendations regarding sun protective behaviors. PUBLIC HEALTH RELEVANCE: Nevi (moles) are markers of melanoma risk, and in some cases are precursors of melanoma. This project will examine the genetic, environmental, and behavioral risk factors for nevus development in children. Understanding of these factors will lead to a better understanding of melanoma, and may suggest approaches for melanoma prevention or treatment.